Calmodulin is a regulatory component in the function of strialtal dopamine receptors, because it controls the synthesis, metabolism and action of cyclic. The calmodulin content in striatial membranes increases during dopamine receptor supersensitivity elicited by cocaine. In addition, the responsiveness of adenylate cyclase to dopamine stimulation and the apparent number of dopamine recognition sites are increased. Cocaine failed to modify the function of the GTP-binding protein which couples the dopamine recognition sites to adenylate cyclase. The present results suggest that cocaine may interact with postsynaptic membrane proteins and thereby increase the availability of membrane-adenylate cyclase.